title: Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41.
abstract: The distal human intestine harbors trillions of microbes that allow us to extract calories from otherwise indigestible dietary polysaccharides. The products of polysaccharide fermentation include short-chain fatty acids that are ligands for Gpr41, a G protein-coupled receptor expressed by a subset of enteroendocrine cells in the gut epithelium. To examine the contribution of Gpr41 to energy balance, we compared Gpr41-/- and Gpr41+/+ mice that were either conventionally-raised with a complete gut microbiota or were reared germ-free and then cocolonized as young adults with two prominent members of the human distal gut microbial community: the saccharolytic bacterium, Bacteroides thetaiotaomicron and the methanogenic archaeon, Methanobrevibacter smithii. Both conventionally-raised and gnotobiotic Gpr41-/- mice colonized with the model fermentative community are significantly leaner and weigh less than their WT (+/+) littermates, despite similar levels of chow consumption. These differences are not evident when germ-free WT and germ-free Gpr41 knockout animals are compared. Functional genomic, biochemical, and physiologic studies of germ-free and cocolonized Gpr41-/- and +/+ littermates disclosed that Gpr41-deficiency is associated with reduced expression of PYY, an enteroendocrine cell-derived hormone that normally inhibits gut motility, increased intestinal transit rate, and reduced harvest of energy (short-chain fatty acids) from the diet. These results reveal that Gpr41 is a regulator of host energy balance through effects that are dependent upon the gut microbiota.
authors.affiliation: Center for Genome Sciences and Department of Medicine, Washington University School of Medicine, St. Louis, MO 63108, USA.
authors.forename: Buck S
authors.initials: BS
authors.lastname: Samuel
authors.forename: Abdullah
authors.initials: A
authors.lastname: Shaito
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Motoike
authors.forename: Federico E
authors.initials: FE
authors.lastname: Rey
authors.forename: Fredrik
authors.initials: F
authors.lastname: Backhed
authors.forename: Jill K
authors.initials: JK
authors.lastname: Manchester
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hammer
authors.forename: S Clay
authors.initials: SC
authors.lastname: Williams
authors.forename: Jan
authors.initials: J
authors.lastname: Crowley
authors.forename: Masashi
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Gordon
mesh_terms: D050154:Adiposity; D000818:Animals; D001439:Bacteroides; D004734:Energy Metabolism; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005856:Germ-Free Life; D006801:Humans; D041581:Methanobrevibacter; D051379:Mice; D018345:Mice, Knockout; D019894:Peptide YY / Q000032:analysis; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D013559:Symbiosis
chemical_list: C506482:Gpcr41 protein, mouse; D043562:Receptors, G-Protein-Coupled; D019894:Peptide YY